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PMC:7796072 / 1666-16003 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
81 15-26 Species denotes coronavirus Tax:11118
82 84-90 Species denotes people Tax:9606
83 1528-1534 Species denotes people Tax:9606
84 37-45 Disease denotes COVID-19 MESH:C000657245
85 59-67 Disease denotes infected MESH:D007239
86 133-139 Disease denotes deaths MESH:D003643
87 156-164 Disease denotes COVID-19 MESH:C000657245
88 262-268 Disease denotes deaths MESH:D003643
89 362-368 Disease denotes deaths MESH:D003643
90 606-615 Disease denotes infection MESH:D007239
91 620-625 Disease denotes death MESH:D003643
92 715-724 Disease denotes infection MESH:D007239
93 1369-1376 Disease denotes obesity MESH:D009765
94 1378-1386 Disease denotes diabetes MESH:D003920
95 1392-1404 Disease denotes hypertension MESH:D006973
96 1577-1585 Disease denotes COVID-19 MESH:C000657245
97 1972-1980 Disease denotes COVID-19 MESH:C000657245
98 2270-2278 Disease denotes COVID-19 MESH:C000657245
99 2279-2288 Disease denotes infection MESH:D007239
100 2398-2405 Disease denotes COVID19 MESH:C000657245
101 2448-2458 Disease denotes infections MESH:D007239
104 2677-2680 Gene denotes HbE Gene:3046
105 2685-2703 Disease denotes Thalassemia Traits MESH:D013789
121 3643-3646 Gene denotes HbE Gene:3046
122 3857-3860 Gene denotes HbE Gene:3046
123 3564-3567 Gene denotes HbE Gene:3046
124 3959-3962 Gene denotes Sri Gene:6717
125 2836-2842 Species denotes people Tax:9606
126 2722-2729 Disease denotes SE Asia MESH:D008133
127 2884-2891 Disease denotes SE Asia MESH:D008133
128 3042-3049 Disease denotes SE Asia MESH:D008133
129 3082-3093 Disease denotes thalassemia MESH:D013789
130 3179-3200 Disease denotes thalassemic syndromes MESH:D061325
131 3213-3225 Disease denotes thalassemias MESH:D013789
132 3380-3394 Disease denotes β-thalassemias MESH:D017086
133 3573-3602 Disease denotes thalassemic symbol of SE Asia MESH:D013789
134 3819-3826 Disease denotes SE Asia MESH:D008133
135 3828-3839 Disease denotes thalassemia MESH:D013789
138 4042-4045 Gene denotes HbE Gene:3046
139 4065-4073 Disease denotes COVID-19 MESH:C000657245
192 4496-4499 Gene denotes HbE Gene:3046
193 6864-6867 Gene denotes HbE Gene:3046
194 6432-6435 Gene denotes HbE Gene:3046
195 5996-5999 Gene denotes HbE Gene:3046
196 5593-5596 Gene denotes HbE Gene:3046
197 5490-5493 Gene denotes HbE Gene:3046
198 5282-5285 Gene denotes HbE Gene:3046
199 5008-5011 Gene denotes HbE Gene:3046
200 4952-4955 Gene denotes HbE Gene:3046
201 4639-4642 Gene denotes HbE Gene:3046
202 4199-4202 Gene denotes HbE Gene:3046
203 6165-6173 Species denotes patients Tax:9606
204 6233-6238 Species denotes human Tax:9606
205 6239-6251 Species denotes dengue virus Tax:12637
206 6257-6279 Species denotes human coronavirus 229E Tax:11137
207 6556-6564 Species denotes patients Tax:9606
208 4203-4214 Disease denotes thalassemia MESH:D013789
209 4290-4298 Disease denotes COVID-19 MESH:C000657245
210 4299-4309 Disease denotes infections MESH:D007239
211 4341-4349 Disease denotes COVID-19 MESH:C000657245
212 4350-4360 Disease denotes infections MESH:D007239
213 4710-4728 Disease denotes COVID19 infections MESH:C000657245
214 4803-4811 Disease denotes COVID-19 MESH:C000657245
215 4812-4818 Disease denotes deaths MESH:D003643
216 4844-4855 Disease denotes thalassemia MESH:D013789
217 4919-4930 Disease denotes thalassemia MESH:D013789
218 5093-5106 Disease denotes low infection MESH:D007239
219 5111-5116 Disease denotes death MESH:D003643
220 5224-5232 Disease denotes COVID-19 MESH:C000657245
221 5233-5242 Disease denotes infection MESH:D007239
222 5563-5574 Disease denotes thalassemia MESH:D013789
223 5638-5646 Disease denotes COVID-19 MESH:C000657245
224 5689-5694 Disease denotes death MESH:D003643
225 6000-6011 Disease denotes thalassemia MESH:D013789
226 6045-6096 Disease denotes glucose-6-phosphate dehydrogenase (G6PD) deficiency MESH:D005955
227 6150-6164 Disease denotes G6PD-deficient MESH:D005955
228 6280-6289 Disease denotes infection MESH:D007239
229 6324-6333 Disease denotes pneumonia MESH:D011014
230 6350-6359 Disease denotes infection MESH:D007239
231 6709-6717 Disease denotes COVID-19 MESH:C000657245
232 6750-6757 Disease denotes SE Asia MESH:D008133
233 6823-6831 Disease denotes COVID-19 MESH:C000657245
234 6832-6841 Disease denotes infection MESH:D007239
235 6846-6851 Disease denotes death MESH:D003643
236 6868-6879 Disease denotes thalassemia MESH:D013789
237 6974-6982 Disease denotes COVID-19 MESH:C000657245
238 7071-7089 Disease denotes hemoglobinopathies MESH:D006453
239 7140-7148 Disease denotes COVID-19 MESH:C000657245
240 7156-7167 Disease denotes thalassemia MESH:D013789
241 7213-7224 Disease denotes thalassemia MESH:D013789
242 7269-7277 Disease denotes COVID-19 MESH:C000657245
243 7534-7542 Disease denotes COVID-19 MESH:C000657245
245 7648-7651 Gene denotes HbE Gene:3046
261 8296-8299 Gene denotes HbE Gene:3046
262 8366-8369 Gene denotes HbE Gene:3046
263 7750-7753 Gene denotes HbE Gene:3046
264 7902-7914 Species denotes dengue virus Tax:12637
265 7702-7720 Disease denotes thalassemia traits MESH:D013789
266 7778-7786 Disease denotes COVID-19 MESH:C000657245
267 7787-7796 Disease denotes infection MESH:D007239
268 7829-7840 Disease denotes thalassemia MESH:D013789
269 7878-7885 Disease denotes malaria MESH:D008288
270 8019-8027 Disease denotes infected MESH:D007239
271 8056-8074 Disease denotes infectious disease MESH:D003141
272 8317-8324 Disease denotes SE Asia MESH:D008133
273 8410-8418 Disease denotes COVID-19 MESH:C000657245
274 8419-8429 Disease denotes infections MESH:D007239
275 8434-8440 Disease denotes deaths MESH:D003643
312 9816-9823 Gene denotes miR-223 Gene:407008
313 9900-9907 Gene denotes miR-155 Gene:406947
314 10030-10035 Gene denotes BACH1 Gene:571
315 10195-10200 Gene denotes BACH1 Gene:571
316 10228-10244 Gene denotes heme oxygenase-1 Gene:3162
317 10246-10250 Gene denotes HO-1 Gene:3162
318 10325-10345 Gene denotes toll-like receptor 7 Gene:51284
319 10347-10351 Gene denotes TLR7 Gene:51284
320 10881-10885 Gene denotes HO-1 Gene:3162
321 10003-10006 Gene denotes HbE Gene:3046
322 9567-9570 Gene denotes HbE Gene:3046
323 9402-9405 Gene denotes HbE Gene:3046
324 9020-9025 Species denotes human Tax:9606
325 9455-9467 Species denotes dengue virus Tax:12637
326 9670-9682 Species denotes dengue virus Tax:12637
327 10007-10015 Species denotes patients Tax:9606
328 10110-10122 Species denotes dengue virus Tax:12637
329 10473-10481 Species denotes patients Tax:9606
330 10630-10640 Species denotes SARS-CoV-2 Tax:2697049
331 10641-10652 Species denotes coronavirus Tax:11118
332 10833-10841 Species denotes patients Tax:9606
333 8719-8729 Species denotes plasmodium Tax:5833
334 11156-11159 Gene denotes HbE Gene:3046
335 8612-8628 Disease denotes Hemoglobinopathy MESH:D006453
336 8757-8769 Disease denotes thalassemias MESH:D013789
337 9282-9297 Disease denotes virus infection MESH:D001102
338 9331-9338 Disease denotes SE Asia MESH:D008133
339 9386-9397 Disease denotes thalassemia MESH:D013789
340 9991-10002 Disease denotes thalassemia MESH:D013789
341 10361-10382 Disease denotes immunological defects MESH:D007153
342 10494-10502 Disease denotes COVID-19 MESH:C000657245
343 10684-10692 Disease denotes COVID-19 MESH:C000657245
344 10824-10832 Disease denotes COVID-19 MESH:C000657245
345 10938-10946 Disease denotes COVID-19 MESH:C000657245
346 10947-10956 Disease denotes infection MESH:D007239
347 11044-11058 Disease denotes system failure MESH:D012131
359 11498-11501 Gene denotes ABO Gene:28
360 11648-11663 Gene denotes ABO blood group Gene:28
361 12086-12089 Gene denotes HbE Gene:3046
362 11221-11229 Disease denotes COVID-19 MESH:C000657245
363 11333-11344 Disease denotes thalassemia MESH:D013789
364 11397-11404 Disease denotes malaria MESH:D008288
365 11561-11569 Disease denotes COVID-19 MESH:C000657245
366 11570-11579 Disease denotes infection MESH:D007239
367 11760-11768 Disease denotes COVID-19 MESH:C000657245
368 11769-11778 Disease denotes infection MESH:D007239
369 11849-11856 Disease denotes malaria MESH:D008288
373 12245-12256 Disease denotes thalassemia MESH:D013789
374 12288-12296 Disease denotes COVID-19 MESH:C000657245
375 12465-12472 Disease denotes SE Asia MESH:D008133
377 12554-12557 Gene denotes HbE Gene:3046
389 12919-12922 Gene denotes HbE Gene:3046
390 13059-13063 Gene denotes G6PD Gene:2539
391 13068-13083 Gene denotes ABO blood group Gene:28
392 13308-13313 Gene denotes BACH1 Gene:571
393 13314-13318 Gene denotes HO-1 Gene:3162
394 12813-12821 Species denotes patients Tax:9606
395 12783-12791 Disease denotes infected MESH:D007239
396 12797-12805 Disease denotes COVID-19 MESH:C000657245
397 12884-12902 Disease denotes thalassemia traits MESH:D013789
398 12954-12962 Disease denotes infected MESH:D007239
399 13142-13159 Disease denotes COVID-19-infected MESH:C000657245
410 14079-14082 Gene denotes HbE Gene:3046
411 13599-13602 Gene denotes HbE Gene:3046
412 13812-13824 Species denotes dengue virus Tax:12637
413 13693-13700 Disease denotes malaria MESH:D008288
414 13803-13810 Disease denotes malaria MESH:D008288
415 13847-13855 Disease denotes COVID-19 MESH:C000657245
416 13856-13865 Disease denotes infection MESH:D007239
417 14083-14094 Disease denotes thalassemia MESH:D013789
418 14318-14326 Disease denotes COVID-19 MESH:C000657245
419 14327-14336 Disease denotes infection MESH:D007239

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T1 1369-1376 Phenotype denotes obesity http://purl.obolibrary.org/obo/HP_0001513
T2 1392-1404 Phenotype denotes hypertension http://purl.obolibrary.org/obo/HP_0000822
T3 6324-6333 Phenotype denotes pneumonia http://purl.obolibrary.org/obo/HP_0002090

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T14 0-10 Sentence denotes Background
T15 11-144 Sentence denotes The coronavirus pandemic (COVID-19) has to date infected over 60 million people worldwide, causing more than 1.43 million deaths [1].
T16 145-313 Sentence denotes The latest COVID-19 statistics for the Kingdom of Thailand as of November 25, 2020, were 3942 confirmed cases and 60 deaths in a total population of 66.6 million [2,3].
T17 314-492 Sentence denotes These numbers translate to 56.25 cases and 0.86 deaths per million inhabitants, respectively, both being puzzlingly low among countries with reliable statistical information [4].
T18 493-632 Sentence denotes The whole of the Mekong River basin and other Southeast (SE) Asian (SEA) neighbors seems to share Thailand’s low infection and death rates.
T19 633-761 Sentence denotes Myanmar, Laos, Cambodia, and China’s Yunnan province all report similarly minimal infection rates (Table 1, Figures 1, 2) [4,5].
T20 762-874 Sentence denotes Many attribute this low incidence to Thai social and cultural practices promoting an inherent social distancing.
T21 875-975 Sentence denotes When greeting one another, Thais do not shake hands or hug, but use the “wai”, a prayer-like motion.
T22 976-1123 Sentence denotes An outdoor lifestyle combined with mask wearing practices due to pre-existing environmental pollution was already in place before the pandemic [5].
T23 1124-1451 Sentence denotes Thailand’s efficient, robust, and responsive grassroots-level universal health care system, directed by able scientists, has greatly impacted preventive and treatment measures [6] even with a rising prevalence of pre-existing comorbidities like obesity, diabetes, and hypertension in the whole of the Mekong river region [7,8].
T24 1452-1600 Sentence denotes Others might argue that Thailand’s low testing frequency (19 tests per 1000 people) might underestimate the magnitude of the COVID-19 situation [3].
T25 1601-1831 Sentence denotes Here, we need to bear in mind that while all returning residents are tested and quarantined, community testing only occurs when tracing contacts or for symptomatic cases seeking treatment (virtually non-existent in the community).
T26 1832-1986 Sentence denotes Another way of looking at the extent of testing relative to the scale of the outbreak is to ask: how many tests does a country do to find 1 COVID-19 case?
T27 1987-2175 Sentence denotes The WHO has suggested around 10–30 tests per confirmed case as a general benchmark of adequate testing, and the Thai average as of November 5, 2020 was 649.7 tests per 1 positive case [9].
T28 2176-2256 Sentence denotes With her porous land border crossings, Thailand allows for population movements.
T29 2257-2335 Sentence denotes Furthermore, COVID-19 infection rates have increased in its western neighbors.
T30 2336-2412 Sentence denotes Yet Thailand has not seen any increase in the number of local COVID19 cases.
T31 2413-2560 Sentence denotes After several months without local infections, single-digit indigenous re-emergences have died out spontaneously both in Thailand and Vietnam [10].
T32 2561-2659 Sentence denotes Elusive locally-shared, genetic determinants may provide an explanation to the above observations.
T33 2661-2721 Sentence denotes Epidemiology of HbE and Thalassemia Traits in Southeast Asia
T34 2722-2883 Sentence denotes SE Asia is the third most populous region in the world [11], encompassing 10 countries with more than 650 million people inhabiting an area over 4.5 million km2.
T35 2884-2991 Sentence denotes SE Asia is a genetic cauldron of different ethnicities descending from diverse and complex origins [11,12].
T36 2992-3206 Sentence denotes Shaped by local malarial environmental pressures, SE Asia’s common genetic denominator is thalassemia, presenting with over 60 different allelic variants, but mainly dominated by 4 major thalassemic syndromes [13].
T37 3207-3375 Sentence denotes The α-thalassemias, with a gene prevalence approaching 40% in northern Thailand and Laos, are considerably less common in Malaysia and the Philippines (around 5%) [13].
T38 3376-3476 Sentence denotes The β-thalassemias showing local variations in genetic prevalence account for up to 9% of all cases.
T39 3477-3563 Sentence denotes Thirdly, Hb Constant Spring [CS] is also seen, with gene frequencies of up to 8% [13].
T40 3564-3642 Sentence denotes HbE, the thalassemic symbol of SE Asia, is increasingly encountered worldwide.
T41 3643-3807 Sentence denotes HbE gene prevalence may reach up to 70% locally in northeastern Thailand and and up to 62% at the triple border region between Thailand, Cambodia, and Laos [13–15].
T42 3808-4012 Sentence denotes Apart from SE Asia, thalassemia genes (including HbE) are also present with diminishing gene frequency in Yunnan, Nepal, Northeastern India, Pakistan, Sri Lanka, Bangladesh, Hong Kong, and Taiwan [13–24].
T43 4014-4073 Sentence denotes Epidemiological Evidence of HbE Protection Against COVID-19
T44 4074-4334 Sentence denotes Intriguing epidemiological observations suggest, and biological evidence supports, an inverse correlation between increasing HbE/thalassemia trait prevalence rates and decreased susceptibility to, and fatality from, COVID-19 infections (Table 1, Figures 1, 2).
T45 4335-4577 Sentence denotes Local COVID-19 infections within Thailand vary 6-fold between the northeast (2.84% of total cases) versus the south (19%), in tandem with regional variations in HbE gene frequency (70% in the northeast compared to 12% in the south) [3,13,25].
T46 4578-4754 Sentence denotes Similarly, Malaysia, which borders southern Thailand, has an HbE trait frequency of only 3.8% [26] but reports substantially higher COVID19 infections compared to Thailand [4].
T47 4755-4995 Sentence denotes Interestingly, in Cambodia and Laos (where zero COVID-19 deaths are reported) (Table 1), thalassemia mutation rates are similar to Thailand [13]; for Cambodia, the thalassemia prevalence is 62.7% (HbE being the most prevalent, at 56%) [27].
T48 4996-5152 Sentence denotes In Myanmar (HbE carrier rates vary between 1.9 and 42% depending on ethnic group and geography), low infection and death rates are also seen (Table 1) [28].
T49 5153-5361 Sentence denotes Vietnam and the neighboring Chinese province of Yunnan both report low COVID-19 infection rates, with locally high prevalence of HbE trait in line with other mainland SE Asian nations (Table 1) [15–24,29–31].
T50 5362-5525 Sentence denotes In Vietnam, the Mon-Khmer-speaking ethnic groups are genetically closer to the Thai-Lao-Cambodian border populations and report HbE gene prevalence up to 36% [29].
T51 5526-5719 Sentence denotes Singapore, where the prevalence of β-thalassemia trait is 0.9% and HbE trait is 0.55% [32], was severely hit by COVID-19 compared to neighboring Thailand, but the death rates were very low [4].
T52 5720-5904 Sentence denotes The high number of cases in Singapore seems to stem from clusters in male migrant workers living in close proximity in crowded living quarters, promoting higher infectious spread [33].
T53 5905-6149 Sentence denotes These migrant workers are from various ethnic groups (e.g., Bengali and Tamil) with higher HbE/thalassemia trait prevalence but also higher glucose-6-phosphate dehydrogenase (G6PD) deficiency rates, compared to resident Singaporeans [32,34,35].
T54 6150-6290 Sentence denotes G6PD-deficient patients have been shown to be highly susceptible to enteroviruses, human dengue virus, and human coronavirus 229E infection.
T55 6291-6365 Sentence denotes They also tend to develop severe pneumonia after microbial infection [36].
T56 6366-6594 Sentence denotes Consequently, close proximity overrides the protective effects of HbE and/or selectively potentiates the risk to infect the ones without the hypothetically protective trait, especially from patients carrying a higher viral load.
T57 6595-6729 Sentence denotes Thailand’s and Singapore’s effective 14-day quarantine policy of all arrivals have now virtually eradicated local COVID-19 cases [37].
T58 6730-6936 Sentence denotes In the remainder of SE Asia and South Asian territories, the trend continues with increasing COVID-19 infection and death rates where HbE/thalassemia trait prevalence is low (Table 1, Figures 1, 2) [14–23].
T59 6937-7095 Sentence denotes In Brazil, a country severely hit by COVID-19, despite heavy early Italian migrations, less than 2% of Brazilian blood donors exhibit hemoglobinopathies [38].
T60 7096-7193 Sentence denotes Similarly, Spain, also severely affected by COVID-19, has a thalassemia trait of only 0.92% [39].
T61 7194-7383 Sentence denotes Despite its higher thalassemia trait prevalence, Italy was severely hit by COVID-19, initially in Lombardy, with a traditionally low carrier rate compared to islands and coastal areas [40].
T62 7384-7635 Sentence denotes Greece [40] and Cyprus [41], with an effective lock-down, a distancing strategy, and a higher, homogenous carrier rate, seem to be experiencing lower COVID-19 rates compared to their European peers, even during the second wave (Table 1, Figures 1, 2).
T63 7637-7669 Sentence denotes How is the HbE Trait Protective?
T64 7670-7920 Sentence denotes The hypothesis we posit is that thalassemia traits in general, and particularly HbE, are protective against COVID-19 infection in similar ways to the numerous thalassemia traits conferring protection against malaria [30,42] and the dengue virus [43].
T65 7921-8075 Sentence denotes Herd immunity development traditionally requires that 60% of the population becomes homogeneously infected by or vaccinated against an infectious disease.
T66 8076-8333 Sentence denotes However, recent mathematical models introducing age and activity heterogeneities into population models predict that herd immunity can be achieved at 43% [44], a level substantially lower than the observed prevalence of HbE in some areas of SE Asia [13–15].
T67 8334-8483 Sentence denotes In fact, in countries where the HbE trait is above 43%, the numbers of both COVID-19 infections and deaths have been minimal (Table 1, Figures 1, 2).
T68 8484-8611 Sentence denotes The genetic and molecular mechanisms of this hypothesized protection are as yet elusive, but biological evidence is suggestive.
T69 8612-8738 Sentence denotes Hemoglobinopathy-induced red blood cell structural modifications hinder invasion, growth, and migration of plasmodium [42,45].
T70 8739-8882 Sentence denotes Recent studies in thalassemias have pointed to the involvement of microRNAs (miRNAs) in malarial pathogenesis and anti-plasmodial defense [45].
T71 8883-9146 Sentence denotes MicroRNAs (miRNAs) are 18–25 nucleotide long, small, non-coding RNA molecules whose production is strictly regulated and abundant in all human cells [46]. miRNAs can downregulate gene expression in translational repression and target around 60% of all genes [46].
T72 9147-9271 Sentence denotes They exhibit decisive regulatory functions associated with a variety of disease processes, including microbial defense [46].
T73 9272-9501 Sentence denotes In dengue virus infection, which is perennially endemic in SE Asia, red blood cell precursors in Thai carriers of thalassemia and HbE trait were significantly less susceptible to the dengue virus compared to normal controls [43].
T74 9502-9615 Sentence denotes This was the first report documenting an antiviral effect of the HbE trait akin to its anti-malarial effect [43].
T75 9616-9914 Sentence denotes A large number of miRNAs have also been implicated in dengue virus defense via structural protein integrity alterations inhibiting access of viral replication machinery to the cytoskeletal apparatus (miR-223) [47], but also through modulations of the host immune interferon response (miR-155) [48].
T76 9915-10056 Sentence denotes Remarkably, increased levels of the latter molecule have been reported in β-thalassemia/HbE patients and linked to BACH1 downregulation [49].
T77 10057-10267 Sentence denotes The same miRNA molecule was also reported to inhibit dengue virus replication by inducing antiviral interferon responses through the same BACH1 pathway downregulation and heme oxygenase-1-(HO-1) induction [48].
T78 10268-10508 Sentence denotes Rare putative loss-of-function variants of X-chromosomal toll-like receptor 7 (TLR7) causing immunological defects in type I and II interferon production have been very recently identified in 4 young male patients with severe COVID-19 [50].
T79 10509-10698 Sentence denotes Type I and II interferon (IFN) responses have been implicated in the initiation of an early immune response to clear the SARS-CoV-2 coronavirus and prevent the development of COVID-19 [50].
T80 10699-10880 Sentence denotes Moreover, the addition of interferon beta-1b to other antivirals in the clinical setting was also more effective in treating COVID-19 patients and rendering them noninfectious [51].
T81 10881-11064 Sentence denotes HO-1 pathway derangements have been implicated in severe COVID-19 infection [52] and in causing exhaustion of hematopoietic stem cells, possibly leading to immune system failure [53].
T82 11065-11174 Sentence denotes Similar structural and molecular mechanisms might be operative in immune effector cells of HbE heterozygotes.
T83 11175-11355 Sentence denotes The hypothesized conferred protection against COVID-19 could also derive from local SE Asian HLA-class allotypes, possibly in linkage disequilibrium with the thalassemia mutations.
T84 11356-11526 Sentence denotes Protection from and resistance to severe malaria has been described in association with HLA antigens in the African continent [54,55] and the ABO blood group system [56].
T85 11527-11810 Sentence denotes However, no HLA associations with COVID-19 infection have been noted in a recent report [57] but an association with the ABO blood group system was confirmed, with bearers of the blood group A phenotype showing an increased risk for COVID-19 infection compared to blood group O [58].
T86 11811-11969 Sentence denotes The O phenotype appears protective to malaria [56] and its worldwide distribution seems to have been shaped by the parasite’s selective genetic pressure [56].
T87 11970-12183 Sentence denotes The frequency of the O blood group in Thailand is 40.5% [59] and its relatively high prevalence along with the high HbE heterozygote frequency could further potentiate the hypothesized antiviral protective effect.
T88 12184-12323 Sentence denotes A similarly intriguing hypothesis querying whether Italian β-thalassemia subjects are immunized against COVID-19 has been put forward [60].
T89 12324-12524 Sentence denotes We believe that the diluted carrier population sizes available in southern European countries are not of the magnitude presently observed in SE Asia and could lead to erroneous interpretation [60,61].
T90 12526-12579 Sentence denotes Limitations and Proving the HbE Protection Hypothesis
T91 12580-12722 Sentence denotes We are not claiming causality at this stage but are hypothesizing an interesting association that needs to be tested with regard to causality.
T92 12723-12990 Sentence denotes Simple hemoglobin electrophoresis of the approximately 4000 infected Thai COVID-19 cohort patients as a case control study will reveal whether the prevalence of thalassemia traits in general (and HbE in particular) differs between infected and uninfected populations.
T93 12991-13058 Sentence denotes Advanced molecular analyses can be performed on the affected cases.
T94 13059-13225 Sentence denotes G6PD and ABO blood group analyses could also be performed to elucidate whether the COVID-19-infected cohort has a higher representation of these genetic determinants.
T95 13226-13509 Sentence denotes Furthermore, miRNA analyses and genetic polymorphism and molecular studies of the BACH1/HO-1 pathway and interferons would elucidate the mechanism of resistance and eventually lead to novel treatment modalities via miRNA decoys or miRNA mimetics or interferon administration [46,51].
T96 13511-13522 Sentence denotes Conclusions
T97 13523-13871 Sentence denotes We theorize that another “Amazing Thailand” attribute [62], an evolutionary HbE variant arising in Thailand through natural selection possibly around 2000 years ago in a malaria-endemic region, might hypothetically be providing its carriers survival advantages with resistance to malaria, dengue virus, and possibly also to COVID-19 infection [63].
T98 13872-14037 Sentence denotes Host immune system modulations induce antiviral interferon responses as well as alter structural protein integrity and inhibit cellular access and viral replication.
T99 14038-14110 Sentence denotes These changes are possibly engendered by HbE/thalassemia carrier miRNAs.
T100 14111-14250 Sentence denotes Proving the hypothesis is of importance, as it may shed light on the mechanisms of viral resistance and lead to novel antiviral treatments.
T101 14251-14337 Sentence denotes These developments can guide decision-making and action to prevent COVID-19 infection.